The purpose of this project is to conduct and coordinate interdisciplinary studies on cancer-prone families in order to clarify the role of genetic mechanisms and host-environmental interactions in carcinogenesis. Clinical studies of high-risk families have suggested etiologic relationships between cancers, constellations of which may cluster in individuals (multiple primary neoplasms) or in kindreds (familial neoplastic syndromes). Bedside observations and epidemiologic studies have clarified the nature of a premalignant cutaneous mole pattern with important implications for melanoma etiology and prevention, and an association of polymastia with kidney cancer. Laboratory abnormalities have provided insights into the mechanisms of susceptibility to cancer. Examples are the finding of subclinical immune dysfunction in family members predisposed to lymphoma, melanoma, and some gastrointestinal malignancies; immunogenetic markers in acute and chronic leukemia, Hodgkin's disease, and Waldenstrom's macroglobulinemia; DNA repair defects in familial melanoma and in families prone to a diversity of rare cancers; metabolic defects in familial bladder cancer, cytogenetic abnormalities in kidney cancer families; and in vitro cell kinetic abnormalities in colon cancer-prone individuals.